Effects of OTX008, a galectin-1 inhibitor, on oral squamous cell carcinoma cells in vitro
|dc.identifier.citation||Greer, P. (2018). Effects of OTX008, a galectin-1 inhibitor, on oral squamous cell carcinoma cells in vitro (Thesis, Doctor of Clinical Dentistry). University of Otago. Retrieved from http://hdl.handle.net/10523/8529||en|
|dc.description.abstract||Oral squamous cell carcinoma (OSCC) is a common cancer that is currently associated with significant morbidity and poor mortality, and for which targeted therapeutics have yet to be proved effective. Galectin-1 is a carbohydrate-binding protein that is commonly upregulated in cancers and is associated with increased risks of metastases, promotion of angiogenesis and escape of the immune response. Galectin-1 has been shown to be upregulated in OSCC, and this upregulation is associated with increased invasion and poor prognosis. The aim of this study was to assess whether the small molecule galectin-1 inhibitor, OTX008, could inhibit OSCC cells in vitro, and to investigate how OTX008 affects the expression of a narrow array of genes in OSCC. One normal oral keratinocyte (NOK) cell line and three OSCC cell lines were cultured and the expression of galectin-1 protein in each quantified using an ELISA. All cell lines were found to express galectin-1, and one of the OSCC lines produced significantly more galectin-1 than the NOK cell line at 6, 24 and 48 hours. Quantification of galectin-1 mRNA expression in each cell line confirmed these results. All four cell lines were cultured with three concentrations of galectin-1 (50, 100 and 150 ng/mL) and four concentrations of OTX008 (12.5, 25, 50 and 100 μg/mL), and cell viability was assayed at 24, 48, 72 and 96 hours. Galectin-1 decreased cell viability at 24 hours in two of the OSCC lines, had no effect on the third, and increased cell viability in the NOK cells at 72 hours. OTX008 reduced cell viability in a dose-dependent manner in all cell lines, and this effect increased at each time point during a 96 hour culture period. OTX008 had the greatest effect on cell viability of the OSCC line with the highest galectin-1 levels compared to the other cell lines. Gene expression in OSCC cells following 48 hours of treatment with 25 μg of OTX008 was relatively unaffected, with the exception of expression of c-Fos which was significantly elevated in two of the OSCC cell lines. The results of this study suggest that OTX008 may have therapeutic potential in the treatment of OSCC, possibly through induction of apoptosis via the AP-1 pathway.|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.title||Effects of OTX008, a galectin-1 inhibitor, on oral squamous cell carcinoma cells in vitro|
|thesis.degree.discipline||Sir John Walsh research Institute|
|thesis.degree.name||Doctor of Clinical Dentistry|
|thesis.degree.grantor||University of Otago|
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